• Risk of breast cancer associated with polymorphisms in genes involved in estrogen metabolism and action as measured by personal health history, cancer family history , risk factor history, food frequency questionnaire, and blood sample at study entry [ Designated as safety issue: No ]
  

• Risk biomarkers as measured by nipple aspirate collection at study entry [ Designated as safety issue: No ]
  
• Correlate breast density and polymorphisms in genes associated with estrogen metabolism and action as measured by mammogram at study entry [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the risk of breast cancer associated with polymorphisms in genes involved in estrogen metabolism and action.
• Determine the relationship between susceptibility genotypes and environmental risk factors for each tumor type.
• Determine the biomarkers of breast cancer risk and/or early detection in nipple fluid, blood, and tissues.
• Determine whether breast density and polymorphisms in genes are associated with estrogen metabolism and action.

OUTLINE: Participants donate a blood sample and complete an epidemiological, dietary, and family history questionnaire. Participants who have undergone biopsy or surgery for breast cancer are asked to authorize the use of their tissues.

Participants who have had a routine film screen mammogram within the past year are asked to submit their most recent mammogram for breast density determination.

Participants warm their breasts with a warm moist washcloth over approximately 30 minutes, then undergo nipple fluid aspiration over 15 seconds, up to 5 times per breast. Women who have any active infection or superficial inflammation of the breast or who are currently lactating or less than 6 months post-lactation do not undergo nipple fluid sampling.

Restriction fragment length polymorphism analysis, simple tandem repeat polymorphism analysis, automated fluorescent genotyping, and single-stranded conformation polymorphism analysis are used to test for genes associated with the biosynthesis and metabolism of estrogen (COMT1, CYP1A1, CYP1A2, CYP2D6, CYP2E1, CYP3A4, CYP17, CYP19, EPHX1, EPHX2, NAT1, NAT2, NQO1, AHR, UDPGT, GSTA1, GSTA2, GSTA3, GSTM1, GSTM2, GSTM3, GSTM5, GSTP1, GSTT1, GSTT2, GSTX1, and GSTX2).

Two-dimensional gel electrophoresis, laser capture microdissection, and surface-enhanced laser desorption ionization spectroscopy are used to test for vitamin D receptor and members of the homocysteine/methionine metabolism family, methylenetetrahydrofolate reductase, methionine synthase, and cystathione beta synthase in nipple fluid, blood, and tissue.

Participants do not receive the results of the genetic testing and these results are not kept in their medical records.

PROJECTED ACCRUAL: A total of 3,000 women (1,000 healthy, 1,000 at high risk for breast cancer, and 1,000 with breast cancer) will be accrued for this study.